CAN INSULIN RESISTANCE LEAD TO DEPRESSION AND OTHER MOOD DISORDERS?

Many people experience the signs of common mood disorders such as anxiety and depression without realizing that unstable blood sugar could be the reason. This should not be surprising because glucose is the primary fuel for the brain.

A growing body of research points to a connection between mood and blood-sugar levels. It has been demonstrated that signs of poor sugar control closely resemble mental health issues such as irritability, anxiety, and worry.

Surprisingly, type 2 diabetics are twice as likely to suffer from depression. Also, anxiety diagnoses are 20% more common in people with diabetes.

So, how are glucose levels and insulin resistance associated with mood swings, depression, and emotions? Let's explore.

What Is Insulin Resistance?

Long before a person is diagnosed with type 2 diabetes, the body starts to experience subtle changes. These indications are simultaneously a boon and a bane in that they can enable you to prevent or delay diabetes but may remain undetected due to their subtlety. One of the most significant unnoticed changes is insulin resistance.

Insulin resistance, also known as impaired insulin sensitivity, is a condition where cells in your muscles, fat, and liver do not respond to insulin as they should and are unable to use glucose from your blood for energy. As a result, the pancreas produces more insulin to make up for the loss, and your blood sugar levels rise over time.

High blood pressure, obesity, type 2 diabetes, and high cholesterol are just a few of the issues that are part of insulin resistance syndrome. So, how do you know if you have insulin resistance?

Insulin resistance cannot be detected by how you feel. You must undergo a blood test to determine your blood sugar, fat (triglyceride), and cholesterol (HDL and LDL) levels. Your health care provider will decide if you have insulin resistance based on the signs and symptoms, in addition to:

• Family and personal medical history
• Blood pressure readings of 130/80 or more.
• A waist measurement exceeding 35 inches for women or 40 inches for men.
• Acanthosis nigricans, or dark, velvety skin patches.
• Skin tags.
• A fasting triglyceride level of more than 150 mg/dL.
• A blood sugar level over 100 mg/dL while fasting
• Low HDL Cholesterol levels, below 40 mg/dL for men and 50 mg/dL for women.

Causes Of Insulin Resistance

It is still being researched how insulin resistance develops. However, studies have discovered a number of genes that influence a person's likelihood of developing insulin resistance.

Diabetes and insulin resistance do not necessarily co-occur. Several factors can increase the likelihood of this condition, such as:

1. Inactive lifestyle.

Exercise increases insulin sensitivity and develops muscles that can absorb blood sugar. Conversely, lack of exercise can have the opposite effect and lead to insulin resistance. Additionally, a sedentary lifestyle and a lack of exercise are linked to weight gain, which can also cause insulin resistance.

2. Obesity, particularly excess abdominal fat.

According to studies, belly fat produces hormones and other chemicals that can fuel chronic inflammation in the body. The inflammatory response may contribute to insulin resistance.

3. A high-carbohydrate diet.

Insulin resistance has been linked to a diet high in saturated fats, highly processed foods, and carbohydrates. Highly processed, high-carbohydrate foods are digested quickly by your body, which raises your blood sugar levels. As a result, your pancreas is under additional strain to produce a lot of insulin, which can eventually result in insulin resistance.

4. Gestational diabetes.

In pregnancy, hormones like estrogen, human placental lactogen, and cortisol can block insulin or make it less effective.

5. A history of diabetes in the family.

Diabetes and insulin resistance tends to run in families. A family history of diabetes significantly predicts fasting insulin levels, according to studies.

6. Smoking.

Smoking is a lifestyle choice that may impact insulin resistance either directly or indirectly. It causes the activation of hormones and indirectly leads to insulin resistance. One of the potential mechanisms underlying these theories could be nicotine-induced.

7. Other factors.

The risk of insulin resistance is also increased if you:

• Are of African, Latino, or Native American ancestry.
• Are over 45 years.
• Have health issues such as polycystic ovary syndrome and nonalcoholic fatty liver disease.
• Suffer from a hormonal disorder such as acromegaly or Cushing's syndrome.
• Have sleep apnea and other sleep problems.
• Take drugs such as antipsychotics, steroids, and HIV medications.

Insulin Resistance And How It Is Linked To Mental Health

A 2021 study found that those with insulin resistance are more likely to develop a serious depressive condition. In addition, the research published in the American Journal of Psychiatry states that people with insulin resistance were more at risk of developing depression.

The Netherlands Study of Depression and Anxiety (NESDA) obtained insights from the enrolled participants, monitoring them over nine years.

The study measured three variables that suggest insulin resistance, which are:

1. High-density lipoprotein cholesterol to triglyceride ratio, which the researchers claim has been well-correlated with the gold standard for insulin resistance and is often used in a clinical context.

2. Waist circumference.

3. Blood sugar level, measured as fasting plasma glucose level.

The team included 601 participants in the data analysis who had never previously experienced anxiety or clinical depression. At the initial evaluation and again after two years, the researchers checked the participants' physical measurements, collected lab samples, and screened them for depression and other psychiatric disorders.

After the initial evaluation, the participants underwent follow-up psychiatric evaluations at four, six, and nine years. The fourth edition of "The Diagnostic and Statistical Manual of Mental Disorders," which is a standardized classification system for the diagnosis of mental health conditions, served as the foundation for the team's criteria for diagnosing cases of depression.

The participants' age, gender, level of physical activity, education level, alcohol use, and smoking status were all taken into account by the researchers. The three insulin resistance indicators were all linked to a higher risk of depression, according to their primary analysis.

The researchers also looked at a particular subgroup of people who, at the beginning of the study, had no signs of insulin resistance. However, by the 2-year follow-up, these individuals had prediabetes based on blood glucose levels and other signs of insulin resistance.

At the nine-year follow-up, they discovered that those who had normal levels of plasma glucose at the two-year mark were less likely to have major depression than those who had prediabetes during the first two years of the study.

Brain Insulin Resistance And Depression

The inability of brain cells to respond to insulin activity is known as brain insulin resistance. The hypothalamus, hippocampus, and cortex are where most of the brain's insulin is located, which is controlled by the central nervous system.

Insulin resistance, reward-seeking behavior, depression, obesity, and diabetes have all been linked. In addition, because brain insulin regulates dopaminergic pathways in the brain, problems with insulin signaling also affect dopamine signaling, which in turn affects the reward and motivation systems of the brain. This may result in depression-related symptoms.

People with depression and insulin resistance, for instance, have demonstrated disruptions in the brain's capacity to signal satiation, exhibiting elevated levels of anhedonia (the inability to experience pleasure) and food-seeking behavior.

In addition, studies imply that insulin resistance in the brain may harm the HPA (hypothalamic-pituitary-adrenal) axis, which controls how the brain reacts to stress. Notably, a deficient HPA axis may impair the control of glucocorticoid secretion, which results in abnormal reactions to stress, and support depressive behavior.

According to an animal study, the emotional regulation centers of the brain express insulin receptors, which enable the cells in those areas to take up and use glucose for energy. When these receptors were taken out of mouse brains, the mice started to feel anxious and depressed. The development of insulin resistance may have similar detrimental effects on the brain and contribute to mood disorders.

How To Prevent Insulin Resistance?

You can take the following steps to reduce insulin resistance and keep type 2 diabetes at bay along with depression, mood swings, and emotional issues.

1. Exercise.

Spend five or more days a week engaging in moderate activity for at least 30 minutes, such as brisk walking. Work up to that if you are not currently active.

2. Reach a healthy weight.

Consult your doctor if you are unsure of your ideal weight or how to lose weight. You might also want to consult a certified personal trainer and a nutritionist.

3. Adopt a balanced diet.

Consider consuming a diet rich in fruits, nuts, vegetables, whole grains, beans, fish, and other lean proteins.

4. Consume medication.

To help control your blood sugar, your doctor may recommend metformin (available as Glucophage, Fortamet, Riomet, and Glumetza).

These lifestyle changes, over time, can:

• Increase insulin sensitivity.
• Reduce your blood sugar levels.
• Elevate HDL ("good") cholesterol levels
• Lower the levels of LDL ("bad") cholesterol and triglycerides.
• Bring down blood pressure.

Along with your primary care physician, you might collaborate with other medical professionals such as a nutritionist and an endocrinologist to develop a personalized treatment plan that is most effective for you.

The Bottom Line

Depression and type 2 diabetes are serious conditions strongly correlated with insulin resistance. In addition, several studies have revealed a link between insulin resistance, mood disorders, and glucose dysfunction. Therefore, monitoring glucose levels and preventing insulin resistance may be effective for maintaining mental and emotional well-being.

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References:

• 1. Roy, Tapash, and Cathy E Lloyd. “Epidemiology of depression and diabetes: a systematic review.” Journal of affective disorders vol. 142 Suppl (2012): S8-21. doi:10.1016/S0165-0327(12)70004-6
• 2. Li, C et al. “Diabetes and anxiety in US adults: findings from the 2006 Behavioral Risk Factor Surveillance System.” Diabetic medicine: a journal of the British Diabetic Association vol. 25,7 (2008): 878-81. doi:10.1111/j.1464-5491.2008.02477.x
• 3. The Role of Family History of Diabetes as a Predictor of Insulin Activity in a Sample of Diverse, Normal Weight Children.” The Role of Family History of Diabetes as a Predictor of Insulin Activity in a Sample of Diverse, Normal Weight Children - ScienceDirect, 25 Feb. 2021, https://doi.org/10.1016/j.endmts.2021.100090
• 4. T. Watson, Kathleen, et al. “The American Journal of Psychiatry.” The American Journal of Psychiatry, 23 Sept. 2021, https://doi.org/10.1176/appi.ajp.2021.20101479
• 5. Arnold, Steven E et al. “Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums.” Nature reviews. Neurology vol. 14,3 (2018): 168-181. doi:10.1038/nrneurol.2017.185
• 6. Hamer, Julia A et al. “Brain insulin resistance: A treatment target for cognitive impairment and anhedonia in depression.” Experimental neurology vol. 315 (2019): 1-8. doi:10.1016/j.expneurol.2019.01.016
• 7. Kullmann, Stephanie, et al. “Brain Insulin Resistance at the Crossroads of Metabolic and Cognitive Disorders in Humans.” Physiological reviews vol. 96,4 (2016): 1169-209. doi:10.1152/physrev.00032.2015
• 8. Lyra E Silva, Natalia de M, et al. “Insulin Resistance as a Shared Pathogenic Mechanism Between Depression and Type 2 Diabetes.” Frontiers in psychiatry vol. 10 57. 14 Feb. 2019, doi:10.3389/fpsyt.2019.00057

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